WO2019030419A1

WO2019030419A1 - Method for treating episodes of apnoea and/or hypopnea and system for detecting said episodes

Info

Publication number: WO2019030419A1
Application number: PCT/ES2017/070574
Authority: WO
Inventors: Baldomero FERNÁNDEZ RONDÁN; Víctor Javier MONTERO BLASCO
Original assignee: Torytrans, S.L
Priority date: 2017-08-09
Filing date: 2017-08-09
Publication date: 2019-02-14
Also published as: RU2020105709A3; EP3685744B1; IL272381A; IL272381B1; EP3685744C0; IL272381B2; CA3072297A1; EP3685744A1; JP7125482B2; JP2020530376A; RU2020105709A; RU2769424C2; EP3685744A4; US20200254250A1; US11420060B2

Abstract

To solve the problems of the prior art, the present invention describes a method for treating episodes of apnoea and/or hypopnea, which comprises the steps of: a) detecting or predicting an episode of apnoea and/or hypopnea by means of at least one sensor selected from a respiratory pressure sensor, a pulse oximeter, an acoustic sensor and/or a respiratory temperature sensor; and b) emitting an electrical signal by means of an electrical actuator connected to at least one submental nerve and/or muscle, the electrical signal having a bipolar waveform and a frequency between 5 and 100 Hz.

Description

METHOD OF TREATMENT OF EPISODES OF APNEA AND / OR HIPOPNEA AND SYSTEM FOR THE DETECTION OF SUCH EPISODES

FIELD OF THE INVENTION The present invention provides a method for the treatment of sleep apnea and / or hypopnea syndrome (hereinafter, OSAHS) that is especially advantageous in its use before an episode of distress and / or hypopnea. occur or at the first signs of that episode. Additionally, the present invention discloses a system that allows the predictive detection of episodes of apnea and / or hypopnea for its use, preferably, with said method.

The present invention discloses a portable, wearable, non-invasive system, without the need for surgical intervention, which allows to treat in real time a user who presents episodes of apnea and / or hypopnea and / or. preferably, determine if an episode of apnea and / or hypopnea will occur to proceed with its treatment in real time. BACKGROUND OF THE INVENTION

The disease of OSAHS (obstructive sleep apnea-hypopnea syndrome) is currently under-diagnosed and under-treated. Undiagnosed patients consume many more health resources than those who suffer from OSAHS are well diagnosed and treated. All this makes the SAHOS is considered a public health problem of the first magnitude.

The reference test for the diagnosis of OSAHS is polysomnography, but it is a long, complex and expensive test that requires qualified medical personnel. Additionally, several invasive systems have been developed for the detection of the syndrome by unilateral stimulation of the hypoglossal nerve (NHG) for patients with moderate to severe OSAHS using a neurostimulator that requires a surgical intervention of about 140 minutes for its implantation in the infraclavicular zone, coupled to an intercostal sensor to detect the ventilatory effort and a tunneled electrode to reach the submandibular area and perform the electrical stimulation of the NHG. The device is activated by the patient at bedtime and the discharges occur with every detected ventilatory effort, regardless of whether an apnea and / or hypopnea is occurring or not. On the other hand, Schwartz et al. (Schwartz AR, Barnes M, Hillman D, Malhotra A, Kezirian E, Smith PL et al.) Acute upper airway responses to hypoglossal nerve stimulation during sleep in obstructive sleep apnea Am J Respir Crit Care Med. 2012 Feb 15; 185 (4 ): 420-6.) Reported the effect of incremental stimulation of synchronized NHG with alternate inspirations in 30 patients with SAHS. The maximum inspiratory flow and the inspiratory flow limitation were compared between the stimulated and unstimulated breaths for each level of stimulation. A marked increase of the maximum inspiratory flow was demonstrated without causing awakenings, however, a clear decrease of obstruction to pharyngeal flow could not be observed.

In addition to said invasive systems, the applicant of the present invention discloses in the patent EP2810599 a device and a non-invasive method for the detection of episodes of apnea and / or hypopnea. However, said invention refers to the detection of said episodes of apnea and / or hypopnea by the analysis of acoustic signals once the episode has occurred. Therefore, it lacks the predictability of a future episode to prevent this episode from occurring.

Description of the invention

In order to have a solution to the problems of the prior art, the present invention provides a method of treating episodes of apnea and / or hypopnea, comprising the steps of:

to. detection or prediction of an episode of apnea and / or hypopnea through at least one sensor selected from: a respiratory pressure sensor, a pulsi-oximeter, an acoustic sensor; and / or respiratory temperature

b. emission of an electrical signal by means of an electric actuator associated with at least one muscle and / or submental nerve;

wherein said electrical signal has a bipolar waveform and a frequency between 5Hz and 100Hz.

In a preferred embodiment, the bipolar wave comprises a positive cycle and a negative cycle, additionally, in one example, one of the cycles has a maximum value that is 40% greater than the maximum value of the other cycle. Additionally, the bipolar wave can comprise of delay between cycles of between 0 and 10 ms. As regards the intensities of the bipolar wave, the present invention contemplates a particular embodiment in which said peak-to-peak intensity is in a range between 1 and 20 mA Preferably, the stage to a predictive detection of the episode of apnea and / or hypopnea. A predictive detection in the context of the present invention refers to identifying the event before it happens, that is, in the proximity to the occurrence of an episode. The detection can be carried out, for example, by means of at least one pressure sensor which quantifies the respiratory signal and the storage in a memory of historical values of respiratory signal and comparing the current values with the historical values. Subsequently, a processor can be used to use such comparisons with historical values to determine the possibility of an episode of apnea or hypopnea.

Preferably, the historical values of the respiratory signal comprise a statistical value of the last measurements

On the other hand, the present invention provides a system for predicting episodes of apnea and / or hypopnea characterized in that it comprises:

At least one sensor of a respiratory signal;

A memory arranged to store a series of measurements of the respiratory signal and a temporary identification of each of the measurements; and A processor connected to the memory to access the series of measurements and the respiratory pressure sensor to access the current measurement;

wherein the processor has means for comparison between the data series and the current measurement, means for determining a reduction of the current measurement below a threshold level stored in the memory and means for emitting a treatment signal if the reduction is below the threshold level.

As in the case of the method, the pressure sensor can be a sensor selected from a pressure sensor, a temperature sensor, a pulsi-oximeter, an acoustic sensor and / or a flow sensor.

In a preferred embodiment, the threshold is a dynamic threshold, that is, the threshold can be modified as a function of previous parameters and can, for example, be automatically adjusted to the parameters of each user, that is, the dynamic threshold can be determined by the statistical comparison of a series of measurements in the series. In a preferred embodiment, the system has at least one additional sensor selected from the group consisting of: a pulsi-oximeter, an electromyography sensor, a temperature sensor, a motion sensor and an audio sensor. Additionally, in the memory, in addition to the respiratory pressure measurements, it is possible to store measurements corresponding to at least one additional sensor.

In a particularly preferred embodiment, the processor has correlation means between the respiratory pressure sensor and the at least one sensor. In addition, the processor may comprise correlation means between the measurements of the pressure sensor and the measurements of the at least one sensor stored in the memory. Preferably, the correlation means comprise artificial intelligence means, in this case, said means can be found previously trained to predict a reduction below the threshold level and comprise means of emission of the treatment signal.

In a particular embodiment, the system is a portable system.

Optionally, the reduction of the current measurement is calculated considering historical measurements, for example at least the measurements corresponding to the last 10 seconds or according to the medical criteria established in each case.

One of the advantages of the device according to the present invention is the ability to perform a diagnosis and an adequate treatment by means of a system that lacks invasive sensors.

As for the treatment of the episodes once detected, the present invention contemplates that the treatment signal is sent to an actuator. The actuator may comprise, for example, at least two electrodes. Said electrodes may be arranged to act on the submental morphology associated with OSAHS.

As in the case of the method of the present invention, the treatment signal comprises a pulse that has a positive cycle and a negative cycle. The negative cycle preferably has an area substantially equal to that of the negative cycle although in particular embodiments of the present invention at least one of the cycles has a signal with an amplitude 40% greater than in the other cycle. In addition, the treatment signal can be a train of pulses.

The present invention also discloses a method for detecting episodes of apnea and / or hypopnea characterized in that it comprises the steps of:

i) Measurement by means of at least one pressure sensor that measures the pressure variations of a user's respiratory signal;

ii) Storage in a memory of a series of measurements including a temporary identification of each measurement;

iii) Comparison of the measurement obtained in step i) with at least one measurement obtained from memory

iv) Calculation of the reduction of the current measurement based on the comparison of stage iii)

v) Determination of an episode of apnea and / or hypopnea if the reduction calculated in stage iv) is below a threshold level stored in memory.

BRIEF DESCRIPTION OF THE DRAWINGS

The attached figures show, in an illustrative and non-limiting manner, an exemplary embodiment of the system according to the present invention, in which:

Figure 1 shows an example of embodiment of a system for detection and treatment of apnea and / or hypopnea according to the present invention.

- Figure 2 shows a schematic view in modular form of a system example according to the present invention.

Figure 3 shows an example of a standard pulse of a treatment signal according to the present invention.

Figure 4 shows an example of a treatment signal comprising a train of standard pulses.

Figure 5 shows another example of a treatment signal comprising a pulse train with variable intensity.

Detailed description of an embodiment Figure 1 shows a preferred embodiment of a system according to the present invention in which the system has a sensing module (1) comprising at least one sensor of the respiratory signal of the user in which said sensor is, for example, a pressure sensor that measures the amplitude of the respiratory signal. Furthermore, said sensor is disposed, for example, through a cannula in the nasal cavity of the user and additionally, a sensing module is placed on the arm or in the patient's chest (3) or in any other place.

The pressure sensor measures the respiratory signal of the user (3) by detecting high sensitivity of the pressure variations. In this way disturbances of the environment are avoided and greater reliability in the detection of the respiratory signal is achieved. Examples of said respiratory signal sensors may be based on pressure, temperature and / or flow sensors. In any case, the objective is to determine the characteristics of the user's breathing.

On the other hand, the system has an actuator (2) with means for joining the user (3). In the example of figure 1, the actuator (2) has pins (21) for disposition around the ears of the user (3). In addition, the actuator comprises electrodes (22) to act non-invasively on at least one muscle and / or a nerve of the morphology associated with the user's airway, for example, a submental muscle associated with the respiratory tract.

Additionally, the system has a processor with communication capability with the sensing module (1) and the actuator (3) and will be explained in greater detail with reference to Figure 2.

Figure 2 shows a schematic view in which a processor incorporating a memory and data processing means is arranged. As an input to said processor, the sensing module (1) is provided and, as an output, a signal to the actuator (2) for signal processing, to a display module (8) or to a memory (9) in which they can store data relative to the output signals output. The means of communication of the processor with the actuator are preferably via cables and the means of communication with the sensing module are preferably via cables although completely wireless and partially wired and / or wireless configurations are also contemplated in the present invention. As for the sensing module (1), this may comprise additional sensors that allow improving an eventual prediction / detection of an episode of apnea and / or hypopnea. Specifically, it is contemplated that additional sensors may be available: · Temperature sensor: It allows to measure the variations in temperature of the air flow, data that can be used as a complement or alternative to the data of the respiratory signal. With this variable there is an additional information to be able to use it if it is required in register of variables of the patients in some circumstances. A body temperature sensor would measure the patient's body temperature if equipped.

• Pulsi-oximeter sensor: Allows the measurement of heart rate and oxygen saturation in blood. This measure improves the diagnostic parameters so that together with other variables improve the detection of episodes of apnea and / or hypopnea in some cases. Normally, this measurement is done non-invasively by optical sensors.

• Electro-myocardial raphy sensor: It allows measuring muscle tone of the neck area related to the musculature associated with the respiratory tract. It has utility to monitor the state of the patient's airways for self-adaptation of the stimulation signals to the characteristics and situation of the patient, mainly in the therapeutic training modality.

• Position and movement sensor: It allows to determine the position and movements of the patient, for example by means of a three-dimensional inertial sensor by means of an IMU (acronym of the expression in English Inertial Measurement Unit) or by means of an accelerometer and provides additional data when establishing a processing of the information for the diagnosis, taking into account the mobility and position of the patient at the moment of detecting the episode and throughout his sleep cycle.

• Acoustic sensor: It improves the detection of snoring respiratory sounds and provides additional data on apnea and / or hypopnea. It can be used in certain circumstances to relate it to other variables.

Subsequently the signals coming from the sensors to be used are sent to the processor and, in particular, to an event detection module (4) in which said module analyzes the current signals with respect to previous signals stored in a memory. In particular, the event detection module is provided with a memory in which the signals coming from the sensing module (1) are stored together with data related to the time in which the measurements are taken, for example, the time or some kind of temporary reference. Subsequently the module proceeds to analyze the current data received directly from the sensing module (1) and, by comparison means, compares the series of previous data with the current measurement for, later, by means of determination, calculates whether there is a reduction of the current measurement of respiratory signals below a threshold level stored in memory. It also has means of emitting a treatment signal if the reduction is below the threshold level. Said event detection module can be updated in real time or quasi-real with respect to the measurements made in the user.

If it is determined that there is a reduction below a threshold level for a certain time, this means that the user will soon experience an episode of apnea and / or hypopnea, so that, in an exemplary embodiment, the event is stored current in an event recording module (7). Said thresholds can be predetermined thresholds or can be defined by a calibration procedure to adapt them to the user and, additionally, said detection thresholds can be automatically adapted taking into account previous measurements and adapted to the characteristics of the patient, for example, by means of intelligence algorithms artificial.

Alternatively, the system can have an actuator (2) that exerts on the user, through non-invasive means, an action to, for example, stimulate the morphology involved in the OSHA. Consequently, the processor can have a stimulus generation module (5) which can be said stimuli, for example, signals that control an electric generator connected to the actuator and electrodes for the stimulation of the morphology involved in the OSHA. On the other hand, said outputs of the stimulus generation module can also be sent to a screen (8) for real time viewing and / or stored in an event memory (9).

Additionally, the system can have a remote transmission module (6) that allows the transmission, for example, of the data stored in the event recording module (7) to a remote server such as the server of a medical service. Figure 3 shows an exemplary embodiment of a standard pulse (20) for a processing signal according to the present invention. In particular, the signal of Figure 3 shows the waveform of the standard pulse (20) that contains a positive part of amplitude (Ap), a duration time at half its amplitude (Ti) and a form according to the temporal function (fi (t)), also has a negative part of amplitude (An), a duration time at half its amplitude (T ₂ ) and a form according to the temporal function (f ₂ (t)).

Additionally, the standard pulse (20) may have a period of the signal of the standard pulse or time between repetitive pulses (T), a time between positive pulse and negative pulse (T ₃ ), a cycle time of the positive pattern pulse and negative (T _c ), a pulse-free time at zero between cycles of the standard pulse (T ₄ ), a rise time of the positive pulse (tsi), a positive pulse lowering time of the positive pulse (tbi), a time of rise of the negative pulse (ts2) and a time of descent of the negative pulse (tb2).

The shape of the standard pulse (20) can comprise of a positive wave section and a negative wave section with its zero times distributed so that it has a symmetrical effect, said configuration is especially advantageous since, when sending it to an electrode to act on the submental morphology, it generates a significant opening of the respiratory tract, and avoids gestures of uncomfortable involuntary movements of the lips and chin when receiving the signal of stimulation.

The levels of intensity and frequency of the pulses are designed to produce the desired effect of depth of the wave to reach the muscle or nerve, and effectiveness of the stimulation, and minimize side effects of skin temperature rise and pain and unwanted movements and gestures.

Figure 4 shows an example of an embodiment in which the processing signal comprises a train of standard pulses (TPp) which can be, for example, a continuous train of duration (Tp), of standard pulses (Pp), of amplitude ( Ap) and relaxation time of the train of pulses of duration (Tr). The duration of the pulse train is TPp. In an exemplary embodiment, the treatment signal can be kept continuous, but it could be chosen to apply these interruptions of the standard pulse train, with which an additional parameter is available to improve the efficiency of the stimulation.

In figure 5 a particular embodiment of a treatment signal according to the present invention is represented in which the shape of the progressive variation of intensity of the stimulation wave (VPI) formed by trains of standard pulses (TPp). With the activation signal of the treatment wave (Sa) the stimulation process is initiated. It starts with TPp pattern pulse trains with an initial amplitude (Api) that is lower than the level necessary to produce the opening of the track. This level can rise progressively until reaching the final amplitude of the stimulation wave (Apf). This final amplitude is determined by the resolution of the episode when there is sufficient opening of the airway that is detected by the sensors or by reaching a safety threshold. At this time, the deactivation signal of the treatment wave (Sd) is generated in which the thresholds of initial and final amplitudes are adjusted to the characteristics and condition of the patient.

The incremental increase in the amplitude of the treatment signal is especially relevant in that it allows starting a treatment with a low initial amplitude (Api). In this way, if the treatment is sufficient with this low amplitude and the episode of distress or hypopnea is solved, it is not necessary to increase the intensity of the signal. In this way, it is guaranteed that the treatment is performed with the least possible action on the patient and with the lowest possible energy consumption.

In Figure 5, the duration time of each activation of the treatment wave (Tvi) is determined by the final amplitude of the stimulation wave (Apf) that is described in the previous paragraph.

The times of silence (without signal) of each activation of the stimulation wave (Ts ₂ ) are determined by the time elapsed between the resolution of an episode and the detection of a new episode. In another embodiment of the present invention the times and levels of performance and silence are determined by a training sequence. The envelope shape of the progressive variation of intensity of the stimulation wave (VPI) of figure 5 has a temporal function Fv (t), which is normally a ramp function.

Below is a table with the different episodes that can be detected and / or treated with a device according to the present invention. The table shows the values currently accepted by the medical community. Although the detection parameters are susceptible to change, said changes in the detection parameters can also be modified in a device according to the present invention to accommodate said changes of criteria.

Each of the treatment parameters must be calibrated with respect to the patient and its calibration is performed by configuring the parameters in such a way that they cause the least possible discomfort to the patient and that they open the respiratory tract.

In tests performed with real subjects, this perception or discomfort is practically nil, achieving a very significant opening of the airway. Consequently, a benefit of the patient is obtained causing almost no discomfort.

Claims

1) Method of treatment of episodes of apnea and / or hypopnea that includes the stages of:

b. emission of an electrical signal by means of an electric actuator associated with at least one muscle and / or submental nerve; wherein said electrical signal has a bipolar waveform and a frequency between 5Hz and 100Hz.

2) Method according to claim 1, characterized in that the bipolar wave comprises a positive cycle and a negative cycle. 3) Method according to claim 2, characterized in that one of the cycles has a maximum value that is 40% greater than the maximum value of the other cycle.

4) Method according to any of claims 1 or 2, characterized in that the bipolar wave comprises a positive cycle, a negative cycle and a delay between cycles of between 0 and 10 ms.

5) Method according to any of the preceding claims, characterized in that the peak-to-peak intensity is between 1 and 20 mA. 6) Method according to claim 1, characterized in that step a. it includes a predictive detection of the episode of apnea and / or hypopnea.

7) Method according to claim 6, characterized in that the detection is carried out by means of at least one pressure sensor that quantifies the respiratory signal and the storage in a memory of historical values of respiratory signal and comparing the current values with the historical values. 8) Method according to any of claims 7 or 8, characterized in that the historical values of the respiratory signal comprise a statistical value of the latest measurements. 9) Prediction system of episodes of apnea and / or hypopnea characterized because it comprises:

• At least one sensor of a respiratory signal;

• A memory arranged to store a series of measurements of the respiratory signal and a temporary identification of each of the measurements; Y

· A processor connected to memory to access the series of measurements and the respiratory pressure sensor to access the current measurement; wherein the processor has means for comparison between the data series and the current measurement, means for determining a reduction of the current measurement below a threshold level stored in the memory and means for emitting a treatment signal if the reduction is below the threshold level.

10) System according to any of the preceding claims, characterized in that the pressure sensor is a sensor selected from a pressure sensor, a temperature sensor, a pulsi-oximeter, an acoustic sensor and / or a flow sensor.

1 1) System, according to any of the preceding claims, characterized in that the threshold is a dynamic threshold.

12) System according to claim 1 characterized in that the dynamic threshold is determined by statistical comparison of a series of measurements of the series.

13) System according to any of claims 9 to 12, characterized in that it also comprises at least one additional sensor selected from the group consisting of: a pulsi-oximeter, an electromyography sensor, a temperature sensor, a motion sensor and an audio sensor.

14) System according to claim 9, characterized in that in the memory, in addition to the measurements of respiratory pressure, measurements corresponding to at least one additional sensor are stored. 15) System according to claim 9, characterized in that the processor has correlation means between the respiratory pressure sensor and the at least one sensor.

16) System according to claim 9, characterized in that the processor comprises correlation means between the measurements of the pressure sensor and the measurements of the at least one sensor stored in the memory.

17) System, according to claim 10, characterized in that the correlation means comprise artificial intelligence means.

18) System according to claim 17, characterized in that the correlation means are previously trained to predict a reduction below the threshold level and comprise means of emission of the treatment signal. 19) System according to any of claims 9 to 18, characterized in that the system is a portable system.

20) System according to any of the preceding claims, characterized in that the reduction of the current measurement is calculated considering at least the measurements corresponding to the last 10 seconds.

21) System according to any of claims 9 to 20, characterized in that it lacks invasive sensors. 22) System according to any of claims 9 to 21, characterized in that the processing signal is sent to an actuator.

23) System, according to claim 22, characterized in that the actuator comprises at least two electrodes.

24) System according to claim 23, characterized in that the electrodes are arranged to act on the submental morphology associated with OSAHS.

25) System according to any of claims 9 to 24, characterized in that the treatment signal comprises a pulse that has a positive cycle and a negative cycle. 26) System, according to claim 25 characterized in that the negative cycle has an area substantially equal to that of the negative cycle. 27) System according to any of claims 9 to 24 characterized in that the processing signal is a train of pulses.

28) Method for detecting episodes of apnea and / or hypopnea, characterized in that it comprises the steps of:

i) Measurement by at least one respiratory pressure sensor of a user's pressure;

Storage in a memory of a series of measurements including a temporary identification of each measurement;

Comparison of the measurement obtained in step i) with at least one measurement obtained from memory

Determination of an episode of apnea and / or hypopnea if the reduction calculated in stage iv) is below a threshold level stored in the memory.